ONS Chemotherapy Immunotherapy Certificate 3 major phases of cell division: - ✔Interphase Mitotic phase Cytokinesis 3 steps of interphase: - ✔First growth phase (G1) Synthesis phase (S phase) Second growth phase (G2) 4 phases of mitosis: - ✔Prophase Metaphase Anaphase Telophase Innate immunity: - ✔Non-specific response, either: 1. Barrier (skin, mucous membranes, flora of skin/gut) 2. Cellular components (phagocytes, natural killer cells, granulocytes, macrophages) Adaptive immunity: - ✔Follows innate immunity if unsuccessful. Memory immunity, including: 1. Humoral immunity (production of antibodies or immunoglobulins) 2. Cell mediated immunity (dependent upon T cells) 3. Regulatory T -cells (prevent autoimmune reactions and limit inflammatory responses) Define mutations - ✔Variations in the nucleotide sequence of a gene 3 main goals of treatment: - ✔Cure Control Palliation Define neoadjuvant therapy - ✔Treatment is given prior to surgery to shrink the tumor Define adjuvant therapy - ✔Additional cancer treatment given after the primary treatment to lower the risk that the cancer reoccur Define conditioning/preparative therapy - ✔Treatments used to prepare a patient for stem cell transplantation 2 types of conditioning therapies: - ✔Myeloablative Nonmyeloablative Define dose density - ✔Drug dose per unit of time
Define dose intensity - ✔Amount of drug delivered over time How is relative dose intensity (RDI) calculated? - ✔By comparing the dose that the patient ACTUALLY received to the planned dose of the standard regimen How do alkylating agents work? - ✔By causing a break in the DNA helix strand, interfering with DNA replication and causing cell death 3 subcategories of alkylating agents: - ✔1. Nitrogen mustards 2. Platinum-based agents (do not possess an alkyl group but still termed alkylating agents as they work similarly) 3. Nitrosoureas Most common subcategory of alkylating agents: - ✔Nitrogen mustards Common alkylating agents: - ✔Cyclophosphamide (Cytoxan) Ifosfamide (Ifex) Bendamustine (Treanda) Common platinum-based agents: - ✔Cisplatin (Platinol) Carboplatin (Paraplatin) What is unique about nitrosoureas agents? - ✔Able to cross the blood-brain barrier; can be effective in treating some brain tumors Common nitrosoureas agents: - ✔Carmustine (BiCNU) Lomustine (CeeNu) Streptozocin (Zanosar) Hypersensitivity can occur with late doses of: - ✔Carboplatin These agents are typically categorized as highly emetogenic: - ✔1. Alkylating agents 2. Nitrosoureas Pre-administration labs for alkylating agents and nitrosoureas: - ✔BUN Creatinine CBC w/ diff What is the medication Mesna used for? - ✔Bladder protectant with administration of cyclophosphamide or ifosfamide Instruct pts receiving ________ to avoid exposure to cold air and consuming cold fluids for 3-4 days following treatment - ✔Oxaliplatin
How do antimetabolites function? - ✔By blocking DNA and RNA growth by interfering with enzymes needed for normal cell metabolism Antimetabolites work in the ___ phase. - ✔S What types of cells are best affected by antimetabolites? - ✔Cells with high division rates Common side effects of antimetabolites: - ✔Myelosuppression GI toxicities Photosensitivity Hand-foot syndrome Common antimetabolite drugs: - ✔Azacitidine Capecitabine 5-FU Cytarabine Decitabine Methotrexate The institute for Safe Medication Practices recommends what route of administration for vincristine? - ✔IV piggyback via gravity Anthracycline antitumor abx work by: - ✔Interfering with enzymes necessary for DNA to replicate in ALL phases of the cell cycle The two major classifications of antitumor antibiotics are: - ✔Anthracyclines Non-anthracyclines Common anthracycline antitumor abx: - ✔Daunorubicin Doxorubicin Epirubicin Idarubicin The antitumor abx ___________ is not an anthracycline, but has anthracycline-type properties. - ✔Mitoxantrone Common non-anthracycline antitumor abx: - ✔Actinomycin D Mitomycin C Bleomycin Monitoring necessary with doxorubicin: - ✔Vesicant --> extravasation Cardiac function Lifetime dose tracking (cardiotoxicity)
Lifetime dose of doxorubicin should not exceed: - ✔550 mg/m^2 What cardiac protectant medication can be administered prior to doxorubicin? ✔Dexrazoxane Significant side effects of doxorubicin are: - ✔Cardiotoxicity N/V Mucositis Diarrhea Severe myelosuppression Hepatic impairment Secondary cancers Monitoring necessary with bleomycin: - ✔Pulmonary toxicity Hypersensitivity reactions (esp. in lymphoma patients) Cutaneous reactions Lifetime dose tracking (pulmonary toxicity) Pulmonary fibrosis is possible when the lifetime dose of bleomycin exceeds: - ✔400 units What 6 patient characteristics make CINV more likely? - ✔1. Younger than 50 years 2. Hx of low alcohol intake 3. Female gender 4. Hx of morning sickness during pregnancy 5. Prone to motion sickness 6. Previous chemotherapy Types of CINV: - ✔Acute Delayed Breakthrough Anticipatory Refractory Define acute CINV - ✔Occurring within 24 hours of chemotherapy Define delayed CINV - ✔Occurring from 24 hours to 5 days after treatment Define breakthrough CINV - ✔Occurring despite treatment Define anticipatory CINV - ✔Triggered by taste, odor, memories, visions, or anxiety related to chemotherapy
Define refractory CINV - ✔Occurring during subsequent cycles when treatment failed in earlier cycles Highly emetogenic chemo (HEC) causes CINV in more than ___% of patients - ✔90 Moderately emetogenic chemo (MEC) causes CINV in patients ___% to ___% of the time - ✔30-90 Patients on low-potential emetogenic chemo develop CINV ___% to ___% of the time ✔10-30 Minimal-risk emetogenic chemo causes CINV less than ___% of the time - ✔10 Common IV HEC drugs include: - ✔Carmustine Cisplatin Cyclophosphamide Dacarbazine Mechlorethamine Streptozosin Common IV MEC drugs include: - ✔Carboplatin Cytarabine Daunorubicin Doxorubicin Epirubicin Idarubicin Ifosfamide Irinotecan Oxaliplatin Common low-potential IV emetogenic chemo drugs include: - ✔5-FU Cytarabine Docetaxel Etoposide Gemcitabine Methotrexate Mitomycin C Mitoxantrone Paclitaxel Pemetrexed Common minimal-risk IV emetogenic chemo drugs include: - ✔Bleomycin Bevacizumab Bortezomib Busulfan
Cetuximab Fludarabine Trastuzumab Vinca alkaloids The 2 most important neurotransmitters involved in vomiting are: - ✔1. Serotonin 2. Substance P Describe the peripheral pathway of CINV - ✔Primarily occurs in the GI tract Associated with acute CINV Neurotransmitter --> serotonin Describe the central pathway of CINV - ✔Primarily occurs in the brain Associated with delayed CINV Neurotransmitter --> Substance P Common serotonin 5-HT3 antagonists used for CINV: - ✔Dolasetron Granisetron Ondansetron Palonosetron Common neurokinin-1 antagonists used for CINV: - ✔Aprepitant Fosaprepitant Common steroids used for CINV: - ✔Dexamethasone 2 types of therapies that commonly have cutaneous reactions: - ✔1. EGFR inhibitor therapies 2. Antimetabolites Most-common cutaneous reaction seen with 5-FU and Capecitabine: - ✔Palmar-plantar erythrodysesthesia AKA hand-foot syndrome Antimetabolites that commonly cause cutaneous reactions: - ✔5-FU Capecitabine (Xeloda) Define myelosuppression - ✔Bone marrow activity is decreased, resulting in fewer RBCs, WBCs and platelets If severe: myeloablation The most common dose-limiting toxicity of chemotherapy - ✔Myelosuppression Define nadir, and when does it occur? - ✔The point at which blood cell counts are at their lowest following a treatment cycle.
Typically occurs 7-10 days following cycle NCCN defines neutropenia as an ANC < _______/mm^3 - ✔500 Risk factors for developing neutropenia include: - ✔> 65 years old Hx of neutropenia with previous chemotherapy Hx of chemotherapy or radiation treatment Hematologic malignancy Uncontrolled/advanced cancer Lung cancer Define neutropenic fever - ✔Fever of 101 F or greater one time OR Fever of 100.4 F lasting one hour or longer ANC calculation - ✔(% polys + % bands) x (WBC)/100 Normal WBC count - ✔4,500-10,000 Normal neutrophil count - ✔54%-62% of WBC An ANC of less that _____ is considered a risk for infection - ✔1,000 Define thrombocytopenia - ✔Low platelet count Symptoms of thrombocytopenia - ✔Petechiae or easily bruising Headaches Hypotension and tachycardia Prolonged bleeding (gums, menstruation) Define anemia - ✔Deficiency of RBC or hemoglobin in the blood Symptoms of anemia - ✔Dyspnea Fatigue Dizziness Headaches Acute diarrhea lasts: - ✔1-2 days and resolves on its own Persistent diarrhea lasts: - ✔2-4 weeks Chronic diarrhea lasts: - ✔> 4 weeks
Common constipation-causing agents: - ✔Vinca alkaloids (vincristine and vinorelbine) Thalidomide Lenalidomide Bortezomib Define mucositis - ✔Inflammation of the mucous membranes lining the digestive tract from mouth to anus Define stomatitis - ✔Inflammatory conditions of the mouth specifically AKA oral mucositis Define xerostomia - ✔Dryness of the mouth caused by damage to or dysfunction of the salivary glands Common diarrhea-causing agents: - ✔Irinotecan 5-FU Paclitaxel Dactinomycin Capecitabine Hypersensitivity reaction (HSR) versus anaphylaxis - ✔HSR- localized tissue injury; generalized Anaphylaxis- severe inflammatory response; systemic; caused by histamine release Immediate HSR can occur: - ✔Within 5 minutes of start of infusion to 6 hours following infusion Delayed HSR can occur: - ✔Days or weeks after immediate HSR window Risk factors for HSR and anaphylaxis: - ✔Administration of a known HSR causing agent Hx of allergies Hx of hypersensitivity or anaphylaxis Premedications not ordered/administered First thing to do if a HSR occurs: - ✔STOP THE INFUSION IMMEDIATELY Define cumulative dose - ✔Total dose of an antineoplastic agent or radiation after repeated exposure to the treatment Define single dose - ✔Recommended dose of one antineoplastic agent given at a single point in time
Define course dose (AKA divided dose) - ✔Recommended dose of one antineoplastic agent given over a defined period of time Define extravasation - ✔Leak of a drug capable of causing tissue damage from the intended vessel into the surrounding tissue or unintended sites Agents classified as irritants can cause: - ✔Inflammation Pain Burning ** Rarely cause tissue necrosis comparable to vesicants Agents classified as vesicants can cause: - ✔Blistering Significant pain Tissue damage and destruction **Lead to tissue death Define infiltration - ✔Leakage of non-vesicant/non-irritant solutions into surrounding tissue Common plant alkaloids: - ✔Etoposide Docetaxel Paclitaxel Vinblastine Vinorelbine Vinca alkaloids are ALL administered _(1)_ and should NEVER be administered _(2)_, as this will result in patient death - ✔1. Intravenously 2. Intrathecally How does hormone therapy work? - ✔Attempts to add, block, or remove hormones from the body to interrupt cancer cell division LHRH agonists MOA - ✔Produce an initial increase in LH and FSH, which can cause a flare. Then lower testosterone made by testicles and estrogen & progesterone made by ovaries *Prostate cancer *Estrogen receptor-positive, premenopausal metastatic breat cancer LHRH antagonists MOA - ✔Directly inhibits pituitary from releasing LH and FSH *No tumor flare Most common type of breast cancer - ✔Hormone receptor (HR)-positive breast cancer
Aromatase inhibitors MOA - ✔Block the enzyme aromatase, which turns the hormone androgen into small amounts of estrogen in the body **Less estrogen is available to stimulate growth of HR-positive breast cancer cells 2 types of aromatase inhibitors - ✔1. Steroidal (irreversible) 2. Nonsteroidal (reversible) 3 aromatase inhibitors - ✔Anastrozole Letrozole Exemestane Common side effects of aromatase inhibitors (AI): - ✔Fatigue N/V* Weakness HA* Insomnia Dizziness Hot flashes* Weight gain* Higher cholesterol Increased sweating* Bone/joint pain* Selective ER downregulators (SERDs) MOA - ✔Binding to and degrading ER Common SERD - ✔Fulvestrant Selective ER modulators (SERMs) MOA - ✔Blocking and downregulating ERs *Can function as ER agonists, antagonists, or mixed agonist-antagonists *Can activate or block estrogen Common SERMs - ✔Tamoxifen Raloxifine Bazedoxifine Antiandrogens MOA - ✔Keeps androgens from binding to androgen receptors found in prostate cancer cells (and in some other tissue cells) Androgen synthesis inhibitors MOA - ✔Stop the adrenal glands from producing androgens Common androgen synthesis inhibitors - ✔Ketoconazole Aminoglutethimide
Abiraterone acetate CYP17 inhibitors MOA - ✔Inhibit the key enzyme that catalyzes biosynthesis of androgens from all sources Common CYP17 inhibitors - ✔Abiraterone Orteronel Adrenolytic agents MOA - ✔Suppress testicular and adrenal steroidogenesis, rapidly reducing testosterone levels Define receptor - ✔Molecule inside/on surface of a cell that binds to a specific substance and causes a specific effect in that cell Define monomer - ✔Molecule that can be bonded to other identical molecules to form a polymer Define ligand - ✔Molecule that binds to a receptor to exert a biologic effect Define ligand bonding - ✔Process by which ligand attaches to specific receptor site and activates receptor, activating the signaling pathway Define dimerization - ✔2 monomers that are side-by-side on cell surface are paired and activated by a ligand, which causes a series of signals Define kinase - ✔Enzyme that adds phosphates to other molecules, causing other molecules in the cell to become either active or inactive Define phosphorylation - ✔Activation of a chemical process to initiate signaling Targeted therapies work by: - ✔1. Blocking angiogenesis 2. Blocking signals inside or outside the cell 3. Delivering toxic substances to the cell 4. Simulating the body's immune system __________ has been described as a way to "fire up the immune system's response to cancer" - ✔Immunotherapy Immunotherapy works by the following 3 ways: - ✔1. Stopping or slowing the growth of cancer cells 2. Stopping cancer cells from spreading to other parts of the body 3. Helping the immune system recognize cancer cells and increase its effectiveness at eliminating cancer cells
What sets immunotherapy apart from traditional chemotherapy? - ✔Highly specific Trained to remember cancer cells Immunotherapy categories: - ✔Passive Aggressive Specific Nonspecific Passive immunotherapy MOA - ✔Administered to initiate an antitumor effect *Do not result in any immunologic memory Examples of passive immunotherapy - ✔Monoclonal antibodies Cytokines Active immunotherapy MOA - ✔Mount an immune response against tumor *Should remember cancer cells long after treatment has stopped Examples of active immunotherapy - ✔Cancer vaccines Specific immunotherapy MOA - ✔Target tumor markers or tumor-associated antigens (TAAs) to kill cancer cells Examples of specific immunotherapy - ✔mAbs Cancer vaccines Nonspecific immunotherapy MOA - ✔Stimulate a large immune response *Given adjuvantly to other anticancer treatment drugs Examples of nonspecific immunotherapy - ✔Cytokines, interleukins, checkpoint inhibitors 2 different ways that immunotherapies work against cancer: - ✔1. Triggering the immune system to destroy cancer cells 2. Boost immune system's ability to fight cancer 6 main types of immunotherapy - ✔1. Monoclonal antibodies 2. Immune checkpoint inhibitors 3. Cancer vaccines 4. Nonspecific immunotherapies 5. Adoptive cell therapy (CAR T-cell therapy) 6. Oncolytic virus therapy
mAbs MOA - ✔Mark cancer cell surface receptor/antigen to make the cell visible to the immune system to destroy Different types of mAbs used in treatment of cancer - ✔Naked mAbs Conjugated monoclonal antibodies Bispecific monoclonal antibodies mAbs ending in "-ximab" source - ✔Chimeric human-mouse mAbs ending in "-zumab" source - ✔Humanized mouse mAbs ending in "-umab" source - ✔Fully human mAbs ending in "-omab" source - ✔Murine mouse Immune checkpoint inhibitors MOA - ✔Prevent cancer cells from turning off T cells --> allows T cells to infiltrate a tumor and stop it from growing Immune checkpoint inhibitors initially cause tumors to swell, making it appear as if the tumor is growing. This is called _____________ - ✔Pseudoprogression 2 main types of cancer vaccines - ✔Preventative/prophylactic Treatment/therapeutic Nonspecific immunotherapies MOA - ✔Stimulating the immune system in a general way, hopefully leading to a better immune response against cancer cells Adoptive cell therapy MOA - ✔T cells collected from patient T cells grown in laboratory *This increases amount of T cells able to kill cancer cells or fight infections* T cells given back to patient to help immune system Oncolytic virus therapy MOA - ✔Naturally occurring or genetically engineered virus that can infect and kill a cancer call without harming normal cells Common side effects of immunotherapies - ✔Fatigue Diarrhea Colitis Musculoskeletal pain Dermatitis Common treatment for immunotherapy side effects - ✔Corticosteroids
Results of immunotherapy agents most commonly occur between ____________ after starting therapy - ✔12-16 weeks Hierarchy of controls when controlling workplace hazards - ✔Elimination Substitution Engineering controls Administrative controls PPE 4 different types of medication dosing: - ✔1. Fixed doses 2. Weight-based doses 3. Body surface area (BSA) doses 4. Area under the curve (AUC) doses